Coronin2A links actin-based endosomal processes to the EHD1 fission machinery

Abstract

The mechanisms of endosomal fission are poorly understood. In this study, it was demonstrated that the ATPase EHD1 is linked to the actin cytoskeleton via an interaction with Coronin2A. Depletion of the latter impairs recycling of clathrin-independent cargo and delays internalization of clathrin-dependent cargo by impeding endosomal fission.

Endosomal actin branching, fission and receptor recycling require FCHSD2 recruitment by MICAL-L1

“…Given the ascribed role for MICAL-L1 in endosome fission (Cai et al ., 2014; Farmer et al ., 2020; Rahajeng et al , 2012; Sharma et al ., 2009), we postulated that FCHSD2 may regulate fission at endosomes, potentially through its actin-regulatory activity. In recent years, it has become evident that in addition to punctate endosomes and endosomal carriers, many endosomes and endosomal carriers are tubular and their fission is regulated by MICAL-L1 and its interaction partners (Dhawan et al ., 2020; Dhawan et al , 2022; Farmer et al , 2021; Jones et al , 2020). Accordingly, we asked whether the fission of punctate and tubular-shaped endosomes is impacted by depletion of FCHSD2 (Fig.…”

“…To more definitively quantify the effects of FCHSD2 depletion on endosome fission, we took advantage of a novel in-cell fission assay that we recently developed that uses a synchronized system to acutely measure decrease in endosome size over a 30 min. period (Dhawan et al ., 2022). Briefly, in mock and FCHSD2 knock-down cells, internalized transferrin was used to mark endosomes, and both mock and knock-down cells were incubated with the PI3K inhibitor LY294002 to induce enlarged endosomes and allow synchronization of fission events upon inhibitor washout (chase).…”

“…As a result, this membrane association helps stimulate WASH-mediated ARP2/3 activation of branched actin, leading to further membrane constriction and tubulation, supported by RAB and motor proteins (Farmer et al ., 2020). Ultimately, Coronin 1C (Hoyer et al ., 2018) and 2A (Dhawan et al ., 2022) have been implicated in clearance of branched actin, providing accessibility for the MICAL-L1 partner and fission protein, EHD1, to the membrane, leading to vesicle/tubule release and cargo recycling to the PM. Overall, our study provides new insight into the mechanisms of EE/SE fission, and helps identify how actin-based constriction events are coupled with nucleotide hydrolysis to promote fission.…”

EPLINα controls integrin recycling from Rab21 endosomes to drive breast cancer cell migration

“…The initiation of the early steps of endosome fission requires the WASH complex and activation of Arp2/3-mediated actin branching to drive membrane constriction (40). However, recent findings suggest that the halting of branching nucleation by Arp2/3 inhibition plays an important role in the later steps of fission, allowing access for other players in the fission machinery (41). One such Arp2/3 inhibitor that has been implicated in this process is coronin 1C.…”

Advances and challenges in understanding endosomal sorting and fission

“…To date, it remains unclear if Dynamin2, the GTPase that catalyses fission of clathrin-coated vesicles at the plasma membrane [39,40], is also required for endosomal fission. Although some studies support a role for Dynamin2 in endosomal fission [41][42][43], a wide variety of additional proteins have been implicated in mediating endosomal fission, including branched actin and multiple actin regulators, such as the WASH complex and coronin proteins [43][44][45][46][47][48][49] as well as the endoplasmic reticulum [50]. In addition, tight control of phospholipids and phosphoinositides have been linked to the recruitment of Eps15 homology domain protein-1 (EHD1) [51,52], a key ATPase involved in endosomal fission [53][54][55][56][57].…”